Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses

• Introduction: Among sensitized infants those with high, as compared with low levels, of salivary secretory IgA (SIgA) are less likely to develop allergic symptoms. Also, early colonization with certain gut microbiota, e.g. Lactobacilli and Bifidobacterium species, might be associated with less allergy development. Although animal and in vitro studies emphasize the role of the commensal gut microbiota in the development of the immune system, the influence of the gut microbiota on immune development in infants is unclear. Objective: To assess whether early colonization with certain gut microbiota species associates with mucosal and systemic immune responses i.e. salivary SIgA and the spontaneous toll like receptor (TLR) 2 and TLR4 mRNA expression and LPS-induced cytokine/chemokine responses in peripheral blood mononuclear cells (PBMC). Methods: Faecal samples were collected at one week, one month and two months after birth from 64 Swedish infants, followed prospectively to five years of age. Bacterial DNA was analyzed with real-time PCR using primers binding to Clostridium difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis. Saliva was collected at age six and twelve months and at two and five years and SIgA was measured with ELISA. The PBMC, collected twelve months after birth, were analyzed for TLR2 and TLR4 mRNA expression with real-time PCR. Further, the PBMC were stimulated with LPS and cytokine/chemokine responses were measured with Luminex. Results: The number of Bifidobacterium species in the early faecal samples correlated significantly with the total salivary SIgA levels at six months. Early colonization with Bifidobacterium species, lactobacilli groups or C. difficile did not influence TLR2 and TLR4 expression in PBMC. However, PBMC from infants colonized early with high amounts of Bacteroides fragilis expressed lower levels of TLR4 mRNA spontaneously. Furthermore, LPS-induced production of inflammatory cytokines and chemokines, e.g. IL-6 and CCL4 (MIP-1β), were inversely correlated to the relative amounts of Bacteroides fragilis in the early faecal samples. Conclusion: Bifidobacterial diversity may enhance the maturation of the mucosal SIgA system and early high colonization with Bacteroides fragilis might down-regulate LPS responsiveness in infancy.

Ämnesord

NATURVETENSKAP  -- Biologi -- Immunologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Immunology (hsv//eng)

Nyckelord

Gut microbiota

lactobacilli

bifidobacteria

Clostridium difficile

Bacteroides fragilis

SIgA

TLR2

TLR4

infant

Immunology

Immunologi

immunologi

Immunology

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vet (ämneskategori)

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